Abstract
SummaryBackground. Anlotinib hydrochloride is an oral small molecule inhibitor of multiple tyrosine kinases, and it has been approved as a third-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with other chemotherapy regimens in patients with nonsquamous NSCLC. Methods. This phase I study followed a 3 + 3 dose reduction design with three doses of anlotinib (12 mg, 10 mg, and 8 mg). Anlotinib was given at an initial dose of 12 mg with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results. A total of eight participants were enrolled. Dose-limiting toxicities (DLTs) were observed in two patients (pts) at anlotinib 12 mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred with 10 mg anlotinib, and the MTD was 10 mg. Among seven evaluable pts, four achieved a confirmed partial response (PR), and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95% CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs were observed during the treatment. Conclusion. The feasible dose of anlotinib in combination with platinum/pemetrexed-based chemotherapy as a first-line regimen was 10 mg, which was well tolerated and showed promising antitumor activity in advanced nonsquamous NSCLC.
Highlights
In recent years, various antiangiogenic therapies have been evaluated in combination with platinum-based chemotherapy as a first-line treatment for advanced non-small-cell lung cancer (NSCLC) without driver gene mutations [1, 2]
A total of 8 patients were enrolled in this trial between April 2019 and November 2019
All patients were untreated before enrollment and had histologically confirmed adenocarcinoma without sensitizing EGFR/ALK/ROS1 alterations (Table 1)
Summary
Various antiangiogenic therapies have been evaluated in combination with platinum-based chemotherapy as a first-line treatment for advanced NSCLC without driver gene mutations [1, 2]. Small molecule tyrosine kinase inhibitors (TKIs) with antiangiogenic activity, such as sorafenib, cediranib and vandetanib, have been investigated in Anlotinib is an oral angiokinase inhibitor that blocks VEGFR 1 to 3, platelet-derived growth factor receptor (PDGFR) α and β, and fibroblast growth factor receptor (FGFR) 1 to 4 [6, 7]. With a low half maximal inhibitory concentration ( IC50), anlotinib has shown promising antitumor activity in various tumors, including NSCLC, in previous studies [6, 8], and it is the only CFDA-approved angiokinase inhibitor for advanced NSCLC [9].
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have